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image of Antioxidant Potential of Gallic Acid Prevents Di-2-ethyhexyl Phthalate-induced Inhibition of Osteogenic Differentiation

Abstract

Objective

Di-2-ethylhexylphthalate (DEHP) is utilized as a plasticizer in polyvinylchloride products (PVC). When medical devices like blood bags, tubes, and syringes are employed, DEHP leaches out of the PVC polymers and enters biological fluids through non-covalent binding. The presence of DEHP in peripheral blood leads to contamination of bone marrow. Previous research has demonstrated that this chemical induces oxidative stress, which adversely affects the viability and osteo-differentiation of bone marrow mesenchymal stem cells (BMSCs). Hence, our current study aims to utilize gallic acid (GA), a natural antioxidant, to alleviate the inhibitory effects of DEHP on BMSCs' osteogenic differentiation.

Materials and Methods

In osteogenic media, BMSCs extracted from Wistar rats were treated with 0.25 μM of GA and 100 μM of DEHP individually and in combination for 20 days. Then viability, total protein, malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD), alkaline phosphatase activity, production of collagen1A1 protein as well as expression of Bmp2 and 7, Smad1, Runx2, Oc, Alp, Col-1a1 genes were investigated.

Results

The viability and differentiation ability of BMSCs was significantly (<0.0001) decreased by DEHP, while GA significantly (<0.0001) ameliorated the effect of DEHP. DEHP caused a significant decrease (<0.0001) in the total protein and collagen-1A1 concentration, TAC and activity of antioxidant enzymes, but significantly (<0.001) increased MDA level. In addition, DEHP caused a significant decrease in the expression of osteo-related genes. In the co-treatment group, GA mitigated the toxic effects of DEHP compared to the control group by inhibiting DEHP-induced oxidative stress and enhancing cell viability and osteo-differentiation properties.

Conclusion

These results confirm that GA reduces the negative effects of DEHP on the osteo-differentiation of BMSCs at the cellular level. However, further studies are necessary to validate these findings.

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2025-04-28
2025-09-15
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References

  1. Wianowska D. Olszowy-Tomczyk M. A concise profile of gallic acid—from its natural sources through biological properties and chemical methods of determination. Molecules 2023 28 3 1186 10.3390/molecules28031186 36770851
    [Google Scholar]
  2. Bhuia M.S. Rahaman M.M. Islam T. Bappi M.H. Sikder M.I. Hossain K.N. Akter F. Al Shamsh Prottay A. Rokonuzzman M. Gürer E.S. Calina D. Islam M.T. Sharifi-Rad J. Neurobiological effects of gallic acid: Current perspectives. Chin. Med. 2023 18 1 27 10.1186/s13020‑023‑00735‑7 36918923
    [Google Scholar]
  3. Yang K. Zhang L. Liao P. Xiao Z. Zhang F. Sindaye D. Xin Z. Tan C. Deng J. Yin Y. Deng B. Impact of gallic acid on gut health: Focus on the gut microbiome, immune response, and mechanisms of action. Front. Immunol. 2020 11 580208 10.3389/fimmu.2020.580208 33042163
    [Google Scholar]
  4. Shahrzad S. Aoyagi K. Winter A. Koyama A. Bitsch I. Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans. J. Nutr. 2001 131 4 1207 1210 10.1093/jn/131.4.1207 11285327
    [Google Scholar]
  5. Nayeem N. Smb A. Salem H. Ahel-Alfqy S. Gallic acid: A promising lead molecule for drug development. J. Appl. Pharm. 2016 8 2 1 4 10.4172/1920‑4159.1000213
    [Google Scholar]
  6. Variya B.C. Bakrania A.K. Madan P. Patel S.S. Acute and 28-days repeated dose sub-acute toxicity study of gallic acid in albino mice. Regul. Toxicol. Pharmacol. 2019 101 71 78 10.1016/j.yrtph.2018.11.010 30465803
    [Google Scholar]
  7. Kim S.H. Jun C.D. Suk K. Choi B.J. Lim H. Park S. Lee S.H. Shin H.Y. Kim D.K. Shin T.Y. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol. Sci. 2006 91 1 123 131 10.1093/toxsci/kfj063 16322071
    [Google Scholar]
  8. Tian Q. Wei S. Su H. Zheng S. Xu S. Liu M. Bo R. Li J. Bactericidal activity of gallic acid against multi-drug resistance Escherichia coli. Microb. Pathog. 2022 173 Pt A 105824 10.1016/j.micpath.2022.105824 36243382
    [Google Scholar]
  9. Delfanian M. Sahari M.A. Barzegar M. Ahmadi Gavlighi H. Structure–antioxidant activity relationships of gallic acid and phloroglucinol. J. Food Meas. Charact. 2021 15 6 5036 5046 10.1007/s11694‑021‑01045‑y
    [Google Scholar]
  10. Chaudhary P. Janmeda P. Docea A.O. Yeskaliyeva B. Abdull Razis A.F. Modu B. Calina D. Sharifi-Rad J. Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases. Front Chem. 2023 11 1158198 10.3389/fchem.2023.1158198 37234200
    [Google Scholar]
  11. Yang K. Cao F. Xue Y. Tao L. Zhu Y. Three classes of antioxidant defense systems and the development of postmenopausal osteoporosis. Front. Physiol. 2022 13 840293 10.3389/fphys.2022.840293 35309045
    [Google Scholar]
  12. Kahkeshani N. Farzaei F. Fotouhi M. Alavi S.S. Bahramsoltani R. Naseri R. Momtaz S. Abbasabadi Z. Rahimi R. Farzaei M.H. Bishayee A. Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iran. J. Basic Med. Sci. 2019 22 3 225 237 10.22038/ijbms.2019.32806.7897 31156781
    [Google Scholar]
  13. Oh E. Jeon B. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds. Front. Microbiol. 2015 6 1129 10.3389/fmicb.2015.01129 26528273
    [Google Scholar]
  14. Nemec M.J. Kim H. Marciante A.B. Barnes R.C. Talcott S.T. Mertens-Talcott S.U. Pyrogallol, an absorbable microbial gallotannins-metabolite and mango polyphenols (Mangifera Indica L.) suppress breast cancer ductal carcinoma in situ proliferation in vitro. Food Funct. 2016 7 9 3825 3833 10.1039/C6FO00636A 27491891
    [Google Scholar]
  15. Pandurangan A.K. Mohebali N. Esa N.M. Looi C.Y. Ismail S. Saadatdoust Z. Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: Possible mechanisms. Int. Immunopharmacol. 2015 a 28 2 1034 1043 10.1016/j.intimp.2015.08.019 26319951
    [Google Scholar]
  16. Priscilla D.H. Prince P.S.M. Cardioprotective effect of gallic acid on cardiac troponin-T, cardiac marker enzymes, lipid peroxidation products and antioxidants in experimentally induced myocardial infarction in Wistar rats. Chem. Biol. Interact. 2009 179 2-3 118 124 10.1016/j.cbi.2008.12.012 19146839
    [Google Scholar]
  17. Huang D.W. Chang W.C. Wu J.S.B. Shih R.W. Shen S.C. Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet. Nutr. Res. 2016 36 2 150 160 10.1016/j.nutres.2015.10.001 26547672
    [Google Scholar]
  18. Mansouri M.T. Farbood Y. Sameri M.J. Sarkaki A. Naghizadeh B. Rafeirad M. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food Chem. 2013 138 2-3 1028 1033 10.1016/j.foodchem.2012.11.022 23411210
    [Google Scholar]
  19. Zhang P. Ye J. Dai J. Wang Y. Chen G. Hu J. Hu Q. Fei J. Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss. Front. Endocrinol. (Lausanne) 2022 13 963237 10.3389/fendo.2022.963237 36601012
    [Google Scholar]
  20. Abnosi M.H. Yari S. The toxic effect of gallic acid on biochemical factors, viability and proliferation of rat bone marrow mesenchymal stem cells was compensated by boric acid. J. Trace Elem. Med. Biol. 2018 48 246 253 10.1016/j.jtemb.2018.04.016 29773188
    [Google Scholar]
  21. Abnosi M.H. Sargolzaei J. Nazari F. Gallic acid ameliorates cadmium effect on osteogenesis by activation of alkaline phosphatase and collagen synthesis. Cell J. 2023 25 9 603 612 10.22074/CELLJ.2023.1999110.1263 37718763
    [Google Scholar]
  22. Ito Y. Kamijima M. Nakajima T. Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: A review. Environ. Health Prev. Med. 2019 24 1 47 10.1186/s12199‑019‑0802‑z 31279339
    [Google Scholar]
  23. Horne D.C. Torrance I. Modine T. Gourlay T. The effect of priming solutions and storage time on plasticizer migration in different PVC tubing types--implications for wet storage of ECMO systems. J. Extra Corpor. Technol. 2009 41 4 199 205 10.1051/ject/200941199 20092073
    [Google Scholar]
  24. Henkel C. Lamprecht J. Hüffer T. Hofmann T. Environmental factors strongly influence the leaching of di(2-ethylhexyl) phthalate from polyvinyl chloride microplastics. Water Res. 2023 242 120235 10.1016/j.watres.2023.120235 37348424
    [Google Scholar]
  25. Lozano M. Cid J. DEHP plasticizer and blood bags: Challenges ahead. ISBT Sci. Ser. 2013 8 1 127 130 10.1111/voxs.12027
    [Google Scholar]
  26. Münch F. Göen T. Zimmermann R. Adler W. Purbojo A. Höllerer C. Cesnjevar R.A. Rüffer A. Reduction of exposure to plasticizers in stored red blood cell units. Perfusion 2020 35 1 32 38 10.1177/0267659119851403 31146632
    [Google Scholar]
  27. Calafat A.M. Needham L.L. Silva M.J. Lambert G. Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit. Pediatrics 2004 113 5 e429 e434 10.1542/peds.113.5.e429 15121985
    [Google Scholar]
  28. Brock J.W. Caudill S.P. Silva M.J. Needham L.L. Hilborn E.D. Phthalate monoesters levels in the urine of young children. Bull. Environ. Contam. Toxicol. 2002 68 3 309 314 10.1007/s001280255 11993803
    [Google Scholar]
  29. Karle V.A. Short B.L. Martin G.R. Bulas D.I. Getson P.R. Luban N.L.C. O’Brien A.M. Rubin R.J. Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2-ethylhexyl)phthalate. Crit. Care Med. 1997 25 4 696 703 10.1097/00003246‑199704000‑00023 9142038
    [Google Scholar]
  30. Latini G. Avery G.B. Materials degradation in endotracheal tubes: A potential contributor to bronchopulmonary dysplasia. Acta Paediatr. 1999 88 10 1174 1175 10.1111/j.1651‑2227.1999.tb01011.x 10565474
    [Google Scholar]
  31. Kim Y.M. Kim J. Cheong H.K. Jeon B.H. Ahn K. Exposure to phthalates aggravates pulmonary function and airway inflammation in asthmatic children. PLoS One 2018 13 12 e0208553 10.1371/journal.pone.0208553 30557318
    [Google Scholar]
  32. Green R. Hauser R. Calafat A.M. Weuve J. Schettler T. Ringer S. Huttner K. Hu H. Use of di(2-ethylhexyl) phthalate-containing medical products and urinary levels of mono(2-ethylhexyl) phthalate in neonatal intensive care unit infants. Environ. Health Perspect. 2005 113 9 1222 1225 10.1289/ehp.7932 16140631
    [Google Scholar]
  33. Florencio-Silva R. Sasso G.R.S. Sasso-Cerri E. Simões M.J. Cerri P.S. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. BioMed Res. Int. 2015 2015 1 17 10.1155/2015/421746 26247020
    [Google Scholar]
  34. Abnosi M.H. Aliyari Babolghani Z. Diethylhexyl phthalate induced oxidative stress and caused metabolic imbalance in bone marrow mesenchymal stem cells. Physiol. Pharmacol. 2022 26 1 88 100 10.52547/phypha.26.1.5
    [Google Scholar]
  35. Hussein A.M. Javad S. Zahra S. Induction of caspase-dependent apoptosis in rat bone marrow mesenchymal stem cells due to di-2-ethylhexyl phthalate toxicity was found to arrest the cell cycle at the g1 stage. Curr. Stem Cell Res. Ther. 2023 18 8 1106 1112 10.2174/1574888X18666230106114727 36617713
    [Google Scholar]
  36. Abnosi M.H. Aliyari Babolghani Z. The inhibitory role of di-2-ethylhexyl phthalate on osteogenic differentiation of mesenchymal stem cells via down-regulation of RUNX2 and membrane function impairment. Int. J. Med. Toxicol. Foren. Med. 2020 10 2 26673 10.32598/ijmtfm.v10i2.26673
    [Google Scholar]
  37. Shayeganfar Z. Abnosi M.H. Sargolzaei J. Effect of Di-2-ethylhexylphthalate on alkalinephospatase activity was due to down regulation of osteogenic related genes. Cell Tiss. J. 2023 14 1 80 95 10.61186/JCT.14.1.80
    [Google Scholar]
  38. Chiu C.Y. Sun S.C. Chiang C.K. Wang C.C. Chan D.C. Chen H.J. Liu S.H. Yang R.S. Plasticizer di(2‐ethylhexyl)phthalate interferes with osteoblastogenesis and adipogenesis in a mouse model. J. Orthop. Res. 2018 36 4 1124 1134 10.1002/jor.23740 28921615
    [Google Scholar]
  39. Zhang Y. Zheng L. Cheng D. Lei C. Li H. Zhou J. Zhang C. Song F. Zeng T. Zhao X. Chronic di(2-ethylhexyl) phthalate exposure at environmental-relevant doses induces osteoporosis by disturbing the differentiation of bone marrow mesenchymal stem cells. Sci. Total Environ. 2024 914 169918 10.1016/j.scitotenv.2024.169918 38190899
    [Google Scholar]
  40. Choi J.I. Cho H.H. Effects of Di(2-ethylhexyl)phthalate on Bone Metabolism in Ovariectomized Mice. J. Bone Metab. 2019 26 3 169 177 10.11005/jbm.2019.26.3.169 31555614
    [Google Scholar]
  41. Lai C.C. Liu F.L. Tsai C.Y. Wang S.L. Chang D.M. Di‐(2‐ethylhexyl) phthalate exposure links to inflammation and low bone mass in premenopausal and postmenopausal females: Evidence from ovariectomized mice and humans. Int. J. Rheum. Dis. 2022 25 8 926 936 10.1111/1756‑185X.14386 35855679
    [Google Scholar]
  42. Posnack N.G. Swift L.M. Kay M.W. Lee N.H. Sarvazyan N. Phthalate exposure changes the metabolic profile of cardiac muscle cells. Environ. Health Perspect. 2012 120 9 1243 1251 10.1289/ehp.1205056 22672789
    [Google Scholar]
  43. Rusyn I. Peters J.M. Cunningham M.L. Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Crit. Rev. Toxicol. 2006 36 5 459 479 10.1080/10408440600779065 16954067
    [Google Scholar]
  44. Lin H. Yuan K. Li L. Liu S. Li S. Hu G. Lian Q.Q. Ge R.S. In utero exposure to diethylhexyl phthalate affects rat brain development: A behavioral and genomic approach. Int. J. Environ. Res. Publ. Heal. 2015 12 11 13696 13710 10.3390/ijerph121113696 26516888
    [Google Scholar]
  45. Xu Y. Agrawal S. Cook T.J. Knipp G.T. Di-(2-ethylhexyl)-phthalate affects lipid profiling in fetal rat brain upon maternal exposure. Arch. Toxicol. 2007 81 1 57 62 10.1007/s00204‑006‑0143‑8 16951938
    [Google Scholar]
  46. David R.M. Moore M.R. Finney D.C. Guest D. Chronic toxicity of di(2-ethylhexyl)phthalate in mice. Toxicol. Sci. 2000 58 2 377 385 10.1093/toxsci/58.2.377 11099649
    [Google Scholar]
  47. Moradi M. Parker M. Sneddon A. Lopez V. Ellwood D. Impact of endometriosis on women’s lives: A qualitative study. BMC Womens Health 2014 14 1 123 10.1186/1472‑6874‑14‑123 25280500
    [Google Scholar]
  48. Li L. Liu J.C. Lai F.N. Liu H.Q. Zhang X.F. Dyce P.W. Shen W. Chen H. Di (2-ethylhexyl) phthalate exposure impairs growth of antral follicle in mice. PLoS One 2016 11 2 e0148350 10.1371/journal.pone.0148350 26845775
    [Google Scholar]
  49. David R.M. Proposed mode of action for in utero effects of some phthalate esters on the developing male reproductive tract. Toxicol. Pathol. 2006 34 3 209 219 10.1080/01926230600642625 16698716
    [Google Scholar]
  50. Rowdhwal S.S.S. Chen J. Toxic effects of di-2-ethylhexyl phthalate: An overview. BioMed Res. Int. 2018 2018 1 10 10.1155/2018/1750368 29682520
    [Google Scholar]
  51. Lee J. Lim K.T. Plant‐originated glycoprotein (24 kDa) has an inhibitory effect on proliferation of BNL CL.2 cells in response to di(2‐ethylhexyl)phthalate. Cell Biochem. Funct. 2011 29 6 496 505 10.1002/cbf.1777 21721021
    [Google Scholar]
  52. Rogers R. Ouellet G. Brown C. Moyer B. Rasoulpour T. Hixon M. Cross-talk between the Akt and NF-kappaB signaling pathways inhibits MEHP-induced germ cell apoptosis. Toxicol. Sci. 2008 106 2 497 508 10.1093/toxsci/kfn186 18755736
    [Google Scholar]
  53. Ghosh J. Das J. Manna P. Sil P.C. Hepatotoxicity of di-(2-ethylhexyl)phthalate is attributed to calcium aggravation, ROS-mediated mitochondrial depolarization, and ERK/NF-κB pathway activation. Free Radic. Biol. Med. 2010 49 11 1779 1791 10.1016/j.freeradbiomed.2010.09.011 20854900
    [Google Scholar]
  54. Tetz L.M. Cheng A.A. Korte C.S. Giese R.W. Wang P. Harris C. Meeker J.D. Loch-Caruso R. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro. Toxicol. Appl. Pharmacol. 2013 268 1 47 54 10.1016/j.taap.2013.01.020 23360888
    [Google Scholar]
  55. Wang W. Craig Z.R. Basavarajappa M.S. Hafner K.S. Flaws J.A. Mono-(2-ethylhexyl) phthalate induces oxidative stress and inhibits growth of mouse ovarian antral follicles. Biol. Reprod. 2012 87 6 152 10.1095/biolreprod.112.102467 23077170
    [Google Scholar]
  56. Juan C.A. Pérez de la Lastra J.M. Plou F.J. Pérez-Lebeña E. The chemistry of reactive oxygen species (ROS) revisited: Outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int. J. Mol. Sci. 2021 22 9 4642 10.3390/ijms22094642 33924958
    [Google Scholar]
  57. Gao W. Guo L. Yang Y. Wang Y. Xia S. Gong H. Zhang B.K. Yan M. Dissecting the crosstalk between Nrf2 and NF-κB response pathways in drug-induced toxicity. Front. Cell Dev. Biol. 2022 9 809952 10.3389/fcell.2021.809952 35186957
    [Google Scholar]
  58. Bernatoniene J. Kopustinskiene D.M. The role of catechins in cellular responses to oxidative stress. Molecules 2018 23 4 965 976 10.3390/molecules23040965 29677167
    [Google Scholar]
  59. Oh Y. Ahn C.B. Marasinghe M.P.C.K. Je J.Y. Insertion of gallic acid onto chitosan promotes the differentiation of osteoblasts from murine bone marrow-derived mesenchymal stem cells. Int. J. Biol. Macromol. 2021 183 1410 1418 10.1016/j.ijbiomac.2021.05.122 34022306
    [Google Scholar]
  60. Chen J. Yang J. Ma L. Li J. Shahzad N. Kim C.K. Structure-antioxidant activity relationship of methoxy, phenolic hydroxyl, and carboxylic acid groups of phenolic acids. Sci. Rep. 2020 10 1 2611 10.1038/s41598‑020‑59451‑z 32054964
    [Google Scholar]
  61. Rajan V.K. Muraleedharan K. A computational investigation on the structure, global parameters and antioxidant capacity of a polyphenol, Gallic acid. Food Chem. 2017 220 93 99 10.1016/j.foodchem.2016.09.178 27855941
    [Google Scholar]
  62. Hadidi M. Liñán-Atero R. Tarahi M. Christodoulou M.C. Aghababaei F. The potential health benefits of gallic acid: Therapeutic and food applications. Antioxidants 2024 13 8 1001 10.3390/antiox13081001 39199245
    [Google Scholar]
  63. Guo C. Ding P. Xie C. Ye C. Ye M. Pan C. Cao X. Zhang S. Zheng S. Potential application of the oxidative nucleic acid damage biomarkers in detection of diseases. Oncotarget 2017 8 43 75767 75777 10.18632/oncotarget.20801 29088908
    [Google Scholar]
  64. Bruderer M. Richards R.G. Alini M. Stoddart M.J. Role and regulation of RUNX2 in osteogenesis. Eur. Cell. Mater. 2014 28 269 286 10.22203/eCM.v028a19 25340806
    [Google Scholar]
  65. Hassan M.Q. Tare R.S. Lee S.H. Mandeville M. Morasso M.I. Javed A. van Wijnen A.J. Stein J.L. Stein G.S. Lian J.B. BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J. Biol. Chem. 2006 281 52 40515 40526 10.1074/jbc.M604508200 17060321
    [Google Scholar]
  66. Liu T.M. Lee E.H. Transcriptional regulatory cascades in Runx2-dependent bone development. Tissue Eng. Part B Rev. 2013 19 3 254 263 10.1089/ten.teb.2012.0527 23150948
    [Google Scholar]
  67. Oh Y. Ahn C.B. Je J.Y. Ark shell protein‐derived bioactive peptides promote osteoblastic differentiation through upregulation of the canonical Wnt/β‐catenin signaling in human bone marrow‐derived mesenchymal stem cells. J. Food Biochem. 2020 44 10 e13440 10.1111/jfbc.13440 32808363
    [Google Scholar]
  68. Oh Y. Ahn C.B. Je J.Y. Blue mussel-derived peptides PIISVYWK and FSVVPSPK trigger Wnt/β-catenin signaling-mediated osteogenesis in human bone marrow mesenchymal stem cells. Mar. Drugs 2020 18 10 510 10.3390/md18100510 33050263
    [Google Scholar]
  69. Tao K. Xiao D. Weng J. Xiong A. Kang B. Zeng H. Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt/β-catenin signaling pathway. Toxicol. Lett. 2016 240 1 68 80 10.1016/j.toxlet.2015.10.007 26478571
    [Google Scholar]
  70. Yu A.X.D. Xu M.L. Yao P. Kwan K.K.L. Liu Y.X. Duan R. Dong T.T.X. Ko R.K.M. Tsim K.W.K. Corylin, a flavonoid derived from Psoralea Fructus, induces osteoblastic differentiation via estrogen and Wnt/β‐catenin signaling pathways. FASEB J. 2020 34 3 4311 4328 10.1096/fj.201902319RRR 31965654
    [Google Scholar]
  71. Guo A.J.Y. Choi R.C.Y. Cheung A.W.H. Chen V.P. Xu S.L. Dong T.T.X. Chen J.J. Tsim K.W.K. Baicalin, a flavone, induces the differentiation of cultured osteoblasts: An action via the Wnt/beta-catenin signaling pathway. J. Biol. Chem. 2011 286 32 27882 27893 10.1074/jbc.M111.236281 21652696
    [Google Scholar]
  72. Valenti M. Dalle Carbonare L. Mottes M. Osteogenic differentiation in healthy and pathological conditions. Int. J. Mol. Sci. 2016 18 1 41 10.3390/ijms18010041 28035992
    [Google Scholar]
  73. Blair H.C. Larrouture Q.C. Li Y. Lin H. Beer-Stoltz D. Liu L. Tuan R.S. Robinson L.J. Schlesinger P.H. Nelson D.J. Osteoblast differentiation and bone matrix formation in vivo and in vitro. Tissue Eng. Part B Rev. 2017 23 3 268 280 10.1089/ten.teb.2016.0454 27846781
    [Google Scholar]
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